Water → N-(7-(2-methylthiazol-4-yl)isoquinolin-3-yl)cyclopropanecarboxamide

HRID 1502243Notes

Reaction equation

HRID 1502243 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]3[CH2:17][CH2:16]3)=[O:14])[N:8]=[CH:9]2)=[CH:4][CH:3]=1.[CH3:18][C:19]1[S:20][CH:21]=[C:22](B2OC(C)(C)C(C)(C)O2)[N:23]=1.C(=O)([O-])[O-].[K+].[K+].C(#N)C.O>CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl.ClCCl>[CH3:18][C:19]1[S:20][CH:21]=[C:22]([C:2]2[CH:11]=[C:10]3[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]4[CH2:17][CH2:16]4)=[O:14])[N:8]=[CH:9]3)=[CH:4][CH:3]=2)[N:23]=1

Participants

8

Reactant 5

HCID 962WaterHCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 457863152-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiazoleHCID 67974626N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide

Product 1

HCID 57410128N-(7-(2-methylthiazol-4-yl)isoquinolin-3-yl)cyclopropanecarboxamideYield 21.1%

Reagents, catalysts & solvents 2

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide (101 mg, 0.347 mmol), 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiazole (0.10 g, 0.44 mmol), potassium carbonate (147.9 mg, 1.070 mmol), and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (24.3 mg, 0.0343 mmol) was added acetonitrile (3 mL, 60 mmol) and water (0.3 mL, 20 mmol). The reaction mixture was then stirred in a sealed vial at 90° C. for 8 hours, and then cooled to room temperature. The reaction mixture was poured into dichloromethane, washed once with saturated aqueous NaHCO3, dried over MgSO4, filtered, and evaporated in vacuo. The resulting residue was purified via reverse phase HPLC and lyophilized to yield 22.7 mg (21%) of N-(7-(2-methylthiazol-4-yl)isoquinolin-3-yl)cyclopropanecarboxamide. LCMS (ESI): RT (Min)=4.328, M+H=310.0, method=E; 1H NMR (400 MHz, DMSO-d6) δ 10.89 (s, 1H), 9.20 (s, 1H), 8.60 (s, 1H), 8.45 (s, 1H), 8.24 (dd, J=8.7, 1.5 Hz, 1H), 8.08 (s, 1H), 7.90 (d, J=8.7 Hz, 1H), 2.76 (s, 3H), 2.08 (ddd, J=12.2, 7.8, 4.7 Hz, 1H), 0.85 (dd, J=9.3, 6.3 Hz, 4H).

Workup

  1. temperaturecooled to room temperature
  2. washwashed once with saturated aqueous NaHCO3
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThe resulting residue was purified via reverse phase HPLC

Sources & evidence

ORD record
ord-b23ddef8a2c34737884a8f0b6db6a929
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

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